Ideal body weight-based determination of minimum oral calories beneficial to function and survival in ALS.

Introduction: This study sought to identify the optimal caloric intake to improve function and survival in ALS patients by comparing oral intake per ideal body weight (IBW) and its discrepancy with total energy expenditure (TEE) using the Shimizu formula. Methods: A retrospective analysis of 104 ALS patients was conducted, categorizing them based on their average intake during the first week after admission using two primary intake cutoffs: 25 kcal/kgIBW and 30 kcal/kgIBW. The variance between oral intake and TEE was also evaluated using -300 kcal and 0 kcal as reference points. Results: Oral caloric intake per IBW and functional decline rate (rs = -0.35, p < 0.001), but the variance from TEE was not significantly correlated (-0.11, p = 0.27). Survival data showed that patients consuming less than 25 kcal/kgIBW had a median survival of 24 months, increasing to 38 months for those consuming between 25-30 kcal/kgIBW and 63 months for those consuming 30 kcal/kgIBW or more. Deviations from the TEE did not significantly affect survival (p = 0.36). Among patients consuming less than their TEE, those consuming less than 25 kcal/kgIBW had a shorter median survival (24 months) compared to their counterparts (46 months) (p = 0.022). Consumption of less than 25 kcal/kgBW emerged as a significant negative predictor of patient outcome, independent of factors such as age, gender or disease progression. Discussion: Intakes of 25 kcal/kgIBW or more are correlated with improved ALS outcomes, and larger, multi-regional studies are recommended for deeper insights.

[A case of Neuropsychiatric systemic lupus erythematosus with varying stenotic lesions in several cerebral major arteries and a vertebral artery aneurysm].

A 42 years old female suffered from systemic lupus erythematosus (SLE) about 20 years ago. While steroid was tapered for a steroid-induced psychiatric disorder, she presented with an acute confusional state and was diagnosed with neuropsychiatric SLE (NPSLE). MRI showed acute infarction mainly in the cortex of the right temporal lobe and MRA demonstrated dynamic subacute morphological changes such as stenosis and dilation in several major intracrainal arteries. The right vertebral artery diffusely dilated and subsequently formed an aneurysm in a week. Contrast-enhanced MRI vessel-wall imaging showed a remarkable enhancement of the aneurysm wall, which might indicate an unstable unruptured aneurysm. The prompt introduction of intravenous cyclophosphamide improved both clinical and radiological signs. Our case indicates that intensive immunosuppressive treatments should be considered in NPSLE patients with varying vasospasm and aneurysm, indicating exacerbated disease activity.

Occupational therapy using a robotic-assisted glove ameliorates finger dexterity and modulates functional connectivity in amyotrophic lateral sclerosis.

INTRODUCTION: Although rehabilitation is recommended for amyotrophic lateral sclerosis (ALS), improvement of functional decline has hardly been achieved. We investigated the effect of occupational therapy that uses a robotic-assisted glove (RAG) on hand dexterity and the functional connectivities found in the brain of ALS patients. METHOD: Ten patients diagnosed with ALS and admitted to the Shiga University of Medical Science (SUMS) Hospital from December 2018 to December 2021 participated in the study. These participants chose the hand side to wear RAG and exercised for two weeks. A sham movement was performed on the other side. We administered several functional assessments, including the Simple Test for Evaluating Hand Function (STEF), grip strength, pinch meter for grip strength, Canadian occupational performance measure (COPM), as well as nerve conduction study (NCS) before and after the exercise, and evaluated the results. We also analyzed six patients' resting-state functional magnetic resonance imaging (rs-fMRI). RESULTS: Two-week robotic rehabilitation improved the STEF, grip strength, and COPM scores when compared with those of the other side. However, no significant effect was observed in the pinch meter and the NCS results. The rs-fMRI data analysis revealed that the robotic rehabilitation augmented two functional connectivities between the left pallidum-right supplementary motor cortex and right insular cortex-right sensorimotor network among the patients, which had beneficial effects. CONCLUSION: The occupational therapy using RAG displayed improved hand dexterity. The enhanced functional connectivities around the sensorimotor network might be associated with the improvement in hand dexterity because of the RAG.

Plasma mid-regional pro-adrenomedullin: A biomarker of the ischemic penumbra in hyperacute stroke.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p < 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (rs  = 0.09, p = 0.348), they were higher in HAIS with CDM (n = 34; 0.81 vs. 0.61 nmol/L, p < 0.001) or MDM (n = 26; 0.83 vs. 0.62 nmol/L, p = 0.002). These differences remained significant after adjusting baseline factors (adjusted odds ratio, 4.06 [95% CI, 1.31-12.55], p = 0.015 and 4.65 [1.35-16.11], p = 0.015, respectively). Plasma MR-proADM is elevated in HAIS, especially in those with a substantial penumbra, suggesting potential as a blood biomarker in this region.

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients: The Shiga Stroke and Heart Attack Registry.

BACKGROUND: The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke. METHODS: A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset. RESULTS: A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients. CONCLUSIONS: The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control.

Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism.

The prognostic predictive value of lipid profiling in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we aimed to clarify the value of the levels of serum lipids, including high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), for predicting the prognosis in ALS. This was a single-center retrospective study of 78 patients with ALS. The serum lipid profiles at the first hospital visit after symptom onset were analyzed to determine the correlations of lipids with survival and physical parameters, including nutritional, respiratory, and metabolic conditions. The cutoff level for high HDL was defined as the third quartile, while that of low LDL and TG, as the first quartile. Hypermetabolism was defined as the ratio of resting energy expenditure to lean soft tissue mass ≥ 38 kcal/kg. High HDL was an independent factor for poor prognosis in all patients (hazards ratio [HR]: 9.87, p < 0.001) in the Cox proportional hazard model, including %vital capacity and the monthly decline rate in body mass index and the Revised Amyotrophic Lateral Functional Rating Scale score from symptom onset to diagnosis. Low LDL was a factor for poor prognosis (HR: 6.59, p = 0.017) only in women. Moreover, subgroup analyses with log-rank tests revealed that the prognostic predictive value of high HDL was evident only in the presence of hypermetabolism (p = 0.005). High HDL predicts poor prognosis in all patients, whereas low LDL, only in women. Hypermetabolism and high HDL synergistically augment the negative effect on prognosis.

Factors Affecting Energy Metabolism and Prognosis in Patients with Amyotrophic Lateral Sclerosis.

BACKGROUND/AIMS: Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS. METHODS: Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy). RESULTS: Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (-3.746 to -1.532, p < 0.0001) and percent forced vital capacity (%FVC) (-0.172 to -0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events. CONCLUSIONS: Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass.

Prognostic prediction by hypermetabolism varies depending on the nutritional status in early amyotrophic lateral sclerosis.

To examine whether hypermetabolism could predict the prognosis of early amyotrophic lateral sclerosis (ALS) patients with differing nutritional profiles. This single-center, retrospective study examined the prognosis of ALS patients with hypermetabolism in relation to their nutritional status at hospitalization. The metabolic state was estimated by the ratio of measured resting energy expenditure (mREE) to lean soft tissue mass (LSTM) (mREE/LSTM), wherein patients with ratios ≥ 38 were defined as hypermetabolic. Malnutrition was defined as %ideal body weight < 0.9. Forty-eight patients were enrolled in this study. The hypermetabolic group had shorter survival in the normal-weight group but more prolonged survival in the malnutrition group. Multiplication of nutritional and metabolic factors, such as [(body mass index (BMI) - 19.8) × (mREE/LSTM - 38)], designated as BMI-muscle metabolism index (BMM index), successfully predicted the prognosis in the group with a high BMM index (≥ 1), which showed shorter survival and a faster rate of weight loss and functional decline. Multivariate analysis using the Cox model showed high BMM index was an independent poor prognostic factor (hazard ratio: 4.05; p = 0.025). Prognostic prediction by hypermetabolism varies depending on the nutritional status in ALS, and the BMM index is a consistent prognostic factor.

Online Solid-Phase Extraction-Inductively Coupled Plasma-Quadrupole Mass Spectrometry with Oxygen Dynamic Reaction for Quantification of Technetium-99.

Quantification of pg/L levels (i.e., 0.6 mBq/L) of radioactive technetium-99 (99Tc) was achieved within 15 min in the presence of isobaric and polyatomic interference sources such as ruthenium-99 (99Ru) and molybdenum hydride (98Mo1H) at 3-11 orders of magnitude higher concentrations. Online solid-phase extraction-inductively coupled plasma-quadrupole mass spectrometry (ICP-QMS) with oxygen (O2) dynamic reaction cell (online SPE-ICP-MS-DRC) was shown to be a thorough automatic analytical system, circumventing the need for human handling. At three stepwise separations (SPE-DRC-Q mass filters), we showed that interference materials allowed the coexistence of abundance ratios of 1.5 × 10-13 and 1.1 × 10-5 for 99Tc/Mo and 99Tc/Ru, respectively. A classical mathematical correction using the natural isotope ratio of 99Ru/102Ru was used to calculate the residues of 99Ru. Using this optimized system, a detection limit (DL; 3σ) of 99Tc was 9.3 pg/L (= 5.9 mBq/L) for a 50 mL injection and sequential measurements were undertaken at a cycle of 24 min/sample. For the measurement of a lower concentration of 99Tc, an AG1-X8 anion-exchange column was used to study 20 L of seawater. Its DL was approximately 1000 times greater than that of previous methods (70.0 fg/L). Thus, this method withstands coexistences of 5.8 × 10-18 and 3.5 × 10-9 for 99Tc/Mo and 99Tc/Ru, respectively. Spike and recovery tests were conducted for environmental samples; the resulting values showed good agreement with the spike applied.

[A case of neuro-Behçet's disease triggered by herpes zoster-associated uveitis].

A 69-year-old man was admitted for persistent fever, arthralgia, and visual impairment. Physical examination demonstrated bilateral uveitis and recurrent aphthous stomatitis. The PCR analysis of the aqueous humor of the anterior chamber was positive for the Varicella-zoster virus (VZV). Although no neurological defect was evident, the cerebrospinal fluid contained elevated monocytes but was negative for VZV-PCR. Brain MRI revealed Gd-enhanced lesions in the subcortical white matter, basal ganglia, and cerebellum. With his positive HLAB51, he was diagnosed with neuro-Behcet's disease (NBD) and was successfully treated with high-dose prednisolone. Although the pathogenesis of Behcet's disease is still unknown, the involvement of viral infection is reported. The present case implies that NBD could be triggered by herpes zoster virus associate-uveitis; the accumulation of such cases would help clarify the pathogenesis of Behcet's disease.

Short-Term Effect of Intensive Speech Therapy on Dysarthria in Patients With Sporadic Spinocerebellar Degeneration.

Purpose The aim of this study was to investigate a structured approach for effective speech therapy (ST) for dysarthria and speech-related quality of life in patients with sporadic spinocerebellar degeneration (SCD), including cerebellar-type multiple-system atrophy and cerebellar cortical atrophy. Method Twenty-two patients with SCD (cerebellar-type multiple system atrophy, 15 patients; cerebellar cortical atrophy, seven patients) who underwent intensive ST were examined. Dysarthria was evaluated using the Scale for Assessment and Rating of Ataxia Speech Dysfunction, Assessment of Motor Speech for Dysarthria Articulation, oral diadochokinesis (OD), and Voice Handicap Index-10 (VHI-10). Respiratory muscle strength (inspiratory and expiratory pressure) and respiratory-phonatory coordination (maximum phonation time) were measured. Cognitive function was evaluated using the Montréal Cognitive Assessment and the word fluency test. Mood was evaluated using the Hospital Anxiety and Depression Scale. The relationships between dysarthria scales (particularly, VHI-10) and clinical data were analyzed using stepwise regression. The differences in outcomes after intensive ST were analyzed using the Wilcoxon signed-rank test. The alpha level (p) for statistical significance was set at .0125 by Bonferroni correction. Results For both pre- and post-ST, the patient's OD (p = .002) and maximum phonation time (p = .002) significantly improved, except for Speech Dysfunction scores of the Scale for Assessment and Rating of Ataxia (p = .705) and the VHI-10 (p = .018). The Assessment of Motor Speech for Dysarthria Articulation, OD, and inspiratory pressure were identified as independent variables of VHI-10 (adjusted R 2 = .820) for speech-related quality of life; no correlations among the Montréal Cognitive Assessment, word fluency test, and Hospital Anxiety and Depression Scale scores were observed. Conclusion OD and VHI-10 showed improvements due to changes in speech function and respiratory-phonatory coordination, justifying intensive ST treatment for dysarthria in patients with SCD.

Spinal Muscular Atrophy Type 3 Showing a Specific Pattern of Selective Vulnerability on Muscle Ultrasound.

A 23-year-old woman was admitted for slowly progressive proximal limb muscle weakness from childhood with elevated muscle enzyme levels. Although muscular diseases were suspected, an electromyogram showed remarkable neurogenic changes, and a muscle echogram indicated selective muscle involvement, including dissociation between the soleus and gastrocnemius, which was consistent with previous reports using magnetic resonance imaging (MRI). She was diagnosed with SMA type 3 following genetic testing, and nusinersen was soon initiated. An early diagnosis is mandatory to maximize the benefit of treatment. A muscle echogram may facilitate an early diagnosis in a non-invasive and time-saving manner compared to MRI.

Amelioration of motor and nonmotor symptoms in cortical cerebellar atrophy and multiple system atrophy-cerebellar type by inpatient rehabilitation: a retrospective study.

Sporadic spinocerebellar degenerative diseases such as multiple system atrophy (cerebellar type) and cortical cerebellar atrophy typically present with cerebellar ataxia. Multiple system atrophy is characterized by ataxia, with parkinsonism, dysautonomia and neuropsychiatric symptoms, resulting in reduced quality of life. Effects of physical rehabilitation focused on motor symptoms with ataxia in nonmultiple system atrophy patients have been reported; however, without addressing concomitant nonmotor symptoms. Here, we examined the motor, nonmotor and quality of life effects of inpatient physical rehabilitation in 15 multiple systems atrophy and nine cortical cerebellar atrophy patients without dementia. Rehabilitation involved a 4-week hospitalization with physical, occupational and speech therapy. The following assessments were conducted at admission and discharge: the scale for the assessment and rating of ataxia for ataxia; Montreal cognitive assessment for cognition, hospital anxiety and depression scale for emotion and medical outcomes study short-form for health-related quality of life. Data were analyzed for statistical significance (P < 0.05) using the Wilcoxon signed-rank test. In patients with multiple system atrophy, rehabilitation significantly improved ataxia, cognition with mild cognitive impairment (73.3%) and health-related quality of life; however, patients with depression (86.7%) showed no improvement in emotional health and quality of life. Similar effects on motor and nonmotor symptoms were observed in patients with cortical cerebellar atrophy. This suggests that inpatient rehabilitation could not only improve motor and nonmotor functions, but also the quality of life in patients with spinocerebellar degenerative disease.

Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment.

Large vessel disease and carotid stenosis are key mechanisms contributing to vascular cognitive impairment (VCI) and dementia. Our previous work, and that of others, using rodent models, demonstrated that bilateral common carotid stenosis (BCAS) leads to cognitive impairment via gradual deterioration of the neuro-glial-vascular unit and accumulation of amyloid-ß (Aß) protein. Since brain-wide drainage pathways (glymphatic) for waste clearance, including Aß removal, have been implicated in the pathophysiology of VCI via glial mechanisms, we hypothesized that glymphatic function would be impaired in a BCAS model and exacerbated in the presence of Aß. Male wild-type and Tg-SwDI (model of microvascular amyloid) mice were subjected to BCAS or sham surgery which led to a reduction in cerebral perfusion and impaired spatial learning acquisition and cognitive flexibility. After 3 months survival, glymphatic function was evaluated by cerebrospinal fluid (CSF) fluorescent tracer influx. We demonstrated that BCAS caused a marked regional reduction of CSF tracer influx in the dorsolateral cortex and CA1-DG molecular layer. In parallel to these changes increased reactive astrogliosis was observed post-BCAS. To further investigate the mechanisms that may lead to these changes, we measured the pulsation of cortical vessels. BCAS impaired vascular pulsation in pial arteries in WT and Tg-SwDI mice. Our findings show that BCAS influences VCI and that this is paralleled by impaired glymphatic drainage and reduced vascular pulsation. We propose that these additional targets need to be considered when treating VCI.

The Effect of Intravenous Methylprednisolone on Recurrent Exacerbation in Hematologic Malignancy-associated Progressive Multifocal Leukoencephalopathy.

We herein report a 65-year-old man with progressive multifocal leukoencephalopathy (PML) after 2-year remission from acute myeloid leukemia who developed recurrent episodes of left hemiparesis with gadolinium enhancement on magnetic resonance imaging. Steroid pulse therapy for each exacerbation induced clinical and radiological improvement, suggesting that exacerbations are an excessive immune response to the JC virus and distinct from immune reconstitution inflammatory syndrome (IRIS). Although glucocorticoids are recommended only for IRIS, steroid pulse therapy should be considered as a therapeutic option in cases of exacerbation of hematologic malignancy-associated PML. Importantly, neuroimaging is not sufficient to differentiate excessive inflammation from a controlled inflammatory response, for which steroids are not recommended.

Long-Term Survival after Stroke in 1.4 Million Japanese Population: Shiga Stroke and Heart Attack Registry.

BACKGROUND AND PURPOSE: Although numerous measures for stroke exist, stroke remains one of the leading causes of death in Japan. In this study, we aimed to determine the long-term survival rate after first-ever stroke using data from a large-scale population-based stroke registry study in Japan. METHODS: Part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based registry study of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in Japan. A total 1,880 patients with non-fatal first-ever stroke (among 29-day survivors after stroke onset) registered in 2011 were followed up until December 2016. Five-year cumulative survival rates were estimated using the Kaplan-Meier method, according to subtype of the index stroke. Cox proportional hazards models were used to assess predictors of subsequent all-cause death. RESULTS: During an average 4.3-year follow-up period, 677 patients died. The 5-year cumulative survival rate after non-fatal first-ever stroke was 65.9%. Heterogeneity was present in 5-year cumulative survival according to stroke subtype: lacunar infarction, 75.1%; large-artery infarction, 61.5%; cardioembolic infarction, 44.9%; intracerebral hemorrhage, 69.1%; and subarachnoid hemorrhage, 77.9%. Age, male sex, Japan Coma Scale score on admission, and modified Rankin Scale score before stroke onset were associated with increased mortality during the chronic phase of ischemic and hemorrhagic stroke. CONCLUSIONS: In this study conducted in a real-world setting of Japan, the 5-year survival rate after non-fatal first-ever stroke remained low, particularly among patients with cardioembolic infarction and large-artery infarction in the present population-based stroke registry.